CN106243105B - 亚甲基桥连1,8-萘啶配体及铜(ⅰ)配合物、制备方法和应用 - Google Patents
亚甲基桥连1,8-萘啶配体及铜(ⅰ)配合物、制备方法和应用 Download PDFInfo
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- CN106243105B CN106243105B CN201610679094.9A CN201610679094A CN106243105B CN 106243105 B CN106243105 B CN 106243105B CN 201610679094 A CN201610679094 A CN 201610679094A CN 106243105 B CN106243105 B CN 106243105B
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- VMQMZMRVKUZKQL-UHFFFAOYSA-N Cu+ Chemical compound [Cu+] VMQMZMRVKUZKQL-UHFFFAOYSA-N 0.000 title claims abstract description 48
- 150000005058 1,8-naphthyridines Chemical class 0.000 title claims abstract description 43
- 239000003446 ligand Substances 0.000 title claims abstract description 25
- 238000002360 preparation method Methods 0.000 title claims abstract description 9
- 238000006243 chemical reaction Methods 0.000 claims abstract description 42
- 239000003054 catalyst Substances 0.000 claims abstract description 24
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 claims abstract description 20
- -1 glyoxaline compound Chemical class 0.000 claims abstract description 18
- 150000001502 aryl halides Chemical class 0.000 claims abstract description 17
- 238000005859 coupling reaction Methods 0.000 claims abstract description 12
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims abstract description 3
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 22
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 18
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 15
- 238000000034 method Methods 0.000 claims description 13
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 claims description 12
- 229910052757 nitrogen Inorganic materials 0.000 claims description 12
- 230000015572 biosynthetic process Effects 0.000 claims description 11
- 238000010992 reflux Methods 0.000 claims description 11
- 238000003786 synthesis reaction Methods 0.000 claims description 11
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 10
- 150000002460 imidazoles Chemical class 0.000 claims description 10
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 9
- 238000010499 C–H functionalization reaction Methods 0.000 claims description 7
- 239000013078 crystal Substances 0.000 claims description 7
- 239000005711 Benzoic acid Substances 0.000 claims description 6
- 235000010233 benzoic acid Nutrition 0.000 claims description 6
- 238000001914 filtration Methods 0.000 claims description 6
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 claims description 6
- 239000000047 product Substances 0.000 claims description 6
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Natural products CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 4
- 238000001816 cooling Methods 0.000 claims description 4
- 230000000630 rising effect Effects 0.000 claims description 4
- 238000004809 thin layer chromatography Methods 0.000 claims description 4
- BOSVHBKQNJZNHK-UHFFFAOYSA-N 5,7-dimethyl-1,8-naphthyridin-2-amine Chemical class C1=CC(N)=NC2=NC(C)=CC(C)=C21 BOSVHBKQNJZNHK-UHFFFAOYSA-N 0.000 claims description 3
- 239000006227 byproduct Substances 0.000 claims description 3
- 230000001376 precipitating effect Effects 0.000 claims description 3
- 238000000746 purification Methods 0.000 claims description 3
- 238000005406 washing Methods 0.000 claims description 3
- ZZLCFHIKESPLTH-UHFFFAOYSA-N 4-Methylbiphenyl Chemical compound C1=CC(C)=CC=C1C1=CC=CC=C1 ZZLCFHIKESPLTH-UHFFFAOYSA-N 0.000 claims description 2
- 238000001514 detection method Methods 0.000 claims description 2
- ZHNUHDYFZUAESO-UHFFFAOYSA-N Formamide Chemical compound NC=O ZHNUHDYFZUAESO-UHFFFAOYSA-N 0.000 claims 2
- 239000003795 chemical substances by application Substances 0.000 claims 1
- 125000000118 dimethyl group Chemical group [H]C([H])([H])* 0.000 claims 1
- 150000003457 sulfones Chemical class 0.000 claims 1
- 230000004913 activation Effects 0.000 abstract description 11
- 229910052739 hydrogen Inorganic materials 0.000 abstract description 3
- 239000001257 hydrogen Substances 0.000 abstract description 3
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 abstract description 2
- 239000010949 copper Substances 0.000 description 15
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 12
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 9
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 8
- QARVLSVVCXYDNA-UHFFFAOYSA-N bromobenzene Chemical compound BrC1=CC=CC=C1 QARVLSVVCXYDNA-UHFFFAOYSA-N 0.000 description 8
- 238000006555 catalytic reaction Methods 0.000 description 8
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 6
- 239000007787 solid Substances 0.000 description 6
- 239000002904 solvent Substances 0.000 description 6
- 238000005160 1H NMR spectroscopy Methods 0.000 description 5
- 238000006254 arylation reaction Methods 0.000 description 5
- 229910052802 copper Inorganic materials 0.000 description 5
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 4
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 4
- 239000003513 alkali Substances 0.000 description 4
- XEKOWRVHYACXOJ-UHFFFAOYSA-N ethyl acetate Substances CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 4
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 3
- 238000012512 characterization method Methods 0.000 description 3
- 238000011161 development Methods 0.000 description 3
- 239000003814 drug Substances 0.000 description 3
- 238000002330 electrospray ionisation mass spectrometry Methods 0.000 description 3
- 235000019441 ethanol Nutrition 0.000 description 3
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 3
- 229930014626 natural product Natural products 0.000 description 3
- 239000000843 powder Substances 0.000 description 3
- 239000000758 substrate Substances 0.000 description 3
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
- 238000013459 approach Methods 0.000 description 2
- 230000003197 catalytic effect Effects 0.000 description 2
- 230000008859 change Effects 0.000 description 2
- 238000004440 column chromatography Methods 0.000 description 2
- 238000007796 conventional method Methods 0.000 description 2
- 125000000623 heterocyclic group Chemical group 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 229910052751 metal Inorganic materials 0.000 description 2
- 239000002184 metal Substances 0.000 description 2
- HZVOZRGWRWCICA-UHFFFAOYSA-N methanediyl Chemical compound [CH2] HZVOZRGWRWCICA-UHFFFAOYSA-N 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- UFWIBTONFRDIAS-UHFFFAOYSA-N naphthalene-acid Natural products C1=CC=CC2=CC=CC=C21 UFWIBTONFRDIAS-UHFFFAOYSA-N 0.000 description 2
- 150000005054 naphthyridines Chemical class 0.000 description 2
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 2
- 230000005311 nuclear magnetism Effects 0.000 description 2
- 239000003208 petroleum Substances 0.000 description 2
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 2
- 239000002994 raw material Substances 0.000 description 2
- 230000035484 reaction time Effects 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- 239000000741 silica gel Substances 0.000 description 2
- 229910002027 silica gel Inorganic materials 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 230000007704 transition Effects 0.000 description 2
- 238000010792 warming Methods 0.000 description 2
- ZIFGWWCUONMOLI-UHFFFAOYSA-N 7-methyl-1,8-naphthyridin-2-amine Chemical class C1=CC(N)=NC2=NC(C)=CC=C21 ZIFGWWCUONMOLI-UHFFFAOYSA-N 0.000 description 1
- 238000006443 Buchwald-Hartwig cross coupling reaction Methods 0.000 description 1
- DMBHHRLKUKUOEG-UHFFFAOYSA-N N-phenyl aniline Natural products C=1C=CC=CC=1NC1=CC=CC=C1 DMBHHRLKUKUOEG-UHFFFAOYSA-N 0.000 description 1
- 238000006887 Ullmann reaction Methods 0.000 description 1
- 125000004429 atom Chemical group 0.000 description 1
- 239000002585 base Substances 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 229910052793 cadmium Inorganic materials 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 239000003480 eluent Substances 0.000 description 1
- 125000000524 functional group Chemical group 0.000 description 1
- PCHJSUWPFVWCPO-UHFFFAOYSA-N gold Chemical compound [Au] PCHJSUWPFVWCPO-UHFFFAOYSA-N 0.000 description 1
- 229910052737 gold Inorganic materials 0.000 description 1
- 239000010931 gold Substances 0.000 description 1
- 229910001385 heavy metal Inorganic materials 0.000 description 1
- 125000004435 hydrogen atom Chemical class [H]* 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 229910052742 iron Inorganic materials 0.000 description 1
- 239000006210 lotion Substances 0.000 description 1
- 238000001819 mass spectrum Methods 0.000 description 1
- JKQOBWVOAYFWKG-UHFFFAOYSA-N molybdenum trioxide Chemical compound O=[Mo](=O)=O JKQOBWVOAYFWKG-UHFFFAOYSA-N 0.000 description 1
- 229910052759 nickel Inorganic materials 0.000 description 1
- 150000002894 organic compounds Chemical class 0.000 description 1
- 229910052763 palladium Inorganic materials 0.000 description 1
- 230000005408 paramagnetism Effects 0.000 description 1
- 230000001766 physiological effect Effects 0.000 description 1
- 229910052697 platinum Inorganic materials 0.000 description 1
- 239000010970 precious metal Substances 0.000 description 1
- 239000000376 reactant Substances 0.000 description 1
- 230000009257 reactivity Effects 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 238000004904 shortening Methods 0.000 description 1
- KKCBUQHMOMHUOY-UHFFFAOYSA-N sodium oxide Chemical compound [O-2].[Na+].[Na+] KKCBUQHMOMHUOY-UHFFFAOYSA-N 0.000 description 1
- 229910001948 sodium oxide Inorganic materials 0.000 description 1
- 125000001424 substituent group Chemical group 0.000 description 1
- 125000003107 substituted aryl group Chemical group 0.000 description 1
- 238000010189 synthetic method Methods 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J31/00—Catalysts comprising hydrides, coordination complexes or organic compounds
- B01J31/16—Catalysts comprising hydrides, coordination complexes or organic compounds containing coordination complexes
- B01J31/18—Catalysts comprising hydrides, coordination complexes or organic compounds containing coordination complexes containing nitrogen, phosphorus, arsenic or antimony as complexing atoms, e.g. in pyridine ligands, or in resonance therewith, e.g. in isocyanide ligands C=N-R or as complexed central atoms
- B01J31/1805—Catalysts comprising hydrides, coordination complexes or organic compounds containing coordination complexes containing nitrogen, phosphorus, arsenic or antimony as complexing atoms, e.g. in pyridine ligands, or in resonance therewith, e.g. in isocyanide ligands C=N-R or as complexed central atoms the ligands containing nitrogen
- B01J31/181—Cyclic ligands, including e.g. non-condensed polycyclic ligands, comprising at least one complexing nitrogen atom as ring member, e.g. pyridine
- B01J31/1825—Ligands comprising condensed ring systems, e.g. acridine, carbazole
- B01J31/183—Ligands comprising condensed ring systems, e.g. acridine, carbazole with more than one complexing nitrogen atom, e.g. phenanthroline
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
- C07D233/54—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
- C07D233/56—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, attached to ring carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
- C07D233/54—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
- C07D233/56—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, attached to ring carbon atoms
- C07D233/58—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, attached to ring carbon atoms with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, attached to ring nitrogen atoms
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
- C07D233/54—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
- C07D233/56—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, attached to ring carbon atoms
- C07D233/60—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, attached to ring carbon atoms with hydrocarbon radicals, substituted by oxygen or sulfur atoms, attached to ring nitrogen atoms
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
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- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F1/00—Compounds containing elements of Groups 1 or 11 of the Periodic Table
- C07F1/005—Compounds containing elements of Groups 1 or 11 of the Periodic Table without C-Metal linkages
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- B01J2231/00—Catalytic reactions performed with catalysts classified in B01J31/00
- B01J2231/40—Substitution reactions at carbon centres, e.g. C-C or C-X, i.e. carbon-hetero atom, cross-coupling, C-H activation or ring-opening reactions
- B01J2231/42—Catalytic cross-coupling, i.e. connection of previously not connected C-atoms or C- and X-atoms without rearrangement
- B01J2231/4277—C-X Cross-coupling, e.g. nucleophilic aromatic amination, alkoxylation or analogues
- B01J2231/4283—C-X Cross-coupling, e.g. nucleophilic aromatic amination, alkoxylation or analogues using N nucleophiles, e.g. Buchwald-Hartwig amination
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Abstract
亚甲基桥连1,8‑萘啶配体及铜(Ⅰ)配合物、制备方法和应用，亚甲基桥连1,8‑萘啶配体及铜(Ⅰ)配合物的分子式为：其中R1为氢或甲基。本发明配合物是目前为止发现的第一个在无催化剂条件下通过SP3C―H键活化反应而得到的配合物，首次实现了无催化剂SP3C―H键活化构建C―C键。该铜(Ⅰ)配合物可用作芳基卤化物与咪唑类化合物C―N偶联反应的催化剂，产率高。
Description
技术领域
本发明属于化学技术领域，涉及萘啶配合物。更具体地，涉及亚甲基桥连1,8-萘啶配体及铜(Ⅰ)配合物、制备方法和应用。
背景技术
C―H键是有机化合物中最简单、最常见的官能团，基于C―H键活化策略的化学合成可以简化原料、缩短反应流程，能够实现常规方法难以制备的目标产物，是最经济、最简洁、最高效的途径，符合现代绿色合成化学的发展趋势，因此通过C―H键的活化发展形成C―C、C―X键的合成方法学一直以来受到有机化学家们的广泛关注。但由于C―H键的键能高，极性小，活化困难，反应活性低，非常难以实现有效地转化，使得C―H键的活化成为有机化学家的一大挑战。碳氢键活化是近年来发展迅速的热门领域。碳氢键的直接官能团化反应由于具有多种突出的优点以及很大的挑战性，被誉为“化学的圣杯”，吸引越来越多科学家的关注。在过去的十几年中，经典的贵金属催化的碳氢键活化已取得很大进展，但有毒有害的重金属残留以及较高的成本一直是难以解决的困难。最近，以廉价易得的普通过渡金属催化的碳氢键活化反应，甚至是无过渡金属催化的碳氢键活化反应代表了该领域未来的发展方向，具有重要的战略意义和挑战性，无论在有机化学理论的发展还是在化学工业的应用上都具有及其深远的意义。同时，在实现C―H键活化的同时，如何利用简单的反应物在温和条件下，高原子经济性的实现目标产物合成始终是有机化学家们追求的目标。
此外，有机催化反应在近几年的研究中受到了广泛的关注，相比金属催化而言，它具有低成本，低负载和环境友好的特点。N-杂环化合物及其衍生物作为中间体在生物科学，天然产物和药物中具有广泛应用。N—芳基胺和N—芳基含氮杂环化合物广泛存在于具有生理活性的天然产物中，并广泛应用于医药、生物化学、含氮杂环碳烯化学、有机电致发光、太阳能电池光电转化材料等领域，其合成与应用越来越受到研究者的关注。因此，发展新的方法合成这种含氮化合物在医药化学和有机合成中具有重要的研究意义。目前为止，已知合成C—N键的方法主要包括铜催化的Ullmann偶联反应,Goldberg类型的C—N键形成和钯催化的Buchwald-Hartwig胺化反应,这些反应通常在均相条件下具有较高的收率。用于催化N—芳基化反应的金属主要有Pt、Cu、Fe、Ni、Cd等。由于铜在偶联反应中的活性较高、价格低廉，所以以铜及其盐或氧化物为催化剂的研究最多。
发明内容
本发明要解决的第一个技术问题是在无催化剂条件下通过SP3C―H键活化反应得到亚甲基桥连1,8-萘啶配体及铜(Ⅰ)配合物。
本发明要解决的第二个技术问题是提供亚甲基桥连1,8-萘啶铜(Ⅰ)配合物的制备方法。
本发明要解决的第三个技术问题是提供亚甲基桥连1,8-萘啶铜(Ⅰ)配合物的应用；
为解决上述技术问题，本发明采用下述技术方案：
亚甲基桥连1,8-萘啶配体及铜(Ⅰ)配合物，分子式为：
其中：R1为氢、甲基。
本发明所述的亚甲基桥连1,8-萘啶配体及铜(Ⅰ)配合物的制备方法，包括以下步骤：
1)合成2-甲基-4-R1-7-乙酰氨基-1,8-萘啶：
在圆底烧瓶中加入7-氨基-2,4-二甲基-1,8-萘啶或7-氨基-2-甲基-1,8-萘啶，加入过量乙酸酐，氮气保护下回流2h，薄层色谱检测反应进程，反应液冷却析出黄色晶体，抽滤得到7-乙酰氨基-2,4-甲基-1,8-萘啶或7-乙酰氨基-2-甲基-1,8-萘啶产物，直接用于下面的反应；
2)无催化剂SP3C―H活化合成亚甲基桥连1,8-萘啶配体：
在圆底烧瓶中将7-乙酰氨基-2,4-甲基-1,8-萘啶或7-乙酰氨基-2-甲基-1,8-萘啶和邻醛基苯甲酸溶解在N,N-二甲基甲酰胺中，氮气保护下升温回流反应，薄层色谱检测反应进程，反应完成后将产物纯化，得亚甲基桥连1,8-萘啶配体；
3)合成亚甲基桥连1,8-萘啶铜(Ⅰ)配合物：
将亚甲基桥连1,8-萘啶配体溶于二氯甲烷中，得到A；
将CuI溶于甲醇中，得到B；
将B逐滴加入到A中，氮气保护搅拌反应24小时，得到沉淀，为亚甲基桥连1,8-萘啶铜(Ⅰ)配合物；其中配体和CuI的摩尔比为1:1。
上述方法的步骤1)中，加热回流时间为2小时，氮气保护下继续回流的时间为4小时，回流温度为100-110℃。
步骤1)中，将产物纯化包括：反应液冷却析出黄色晶体或将反应液减压旋蒸除去溶剂，固体残留物用乙醇重结晶，得到7-乙酰氨基-2,4-甲基-1,8-萘啶或7-乙酰氨基-2-甲基-1,8-萘啶。
步骤2)中，先溶解邻醛基苯甲酸，回流后再加入7-乙酰氨基-2,4-甲基-1,8-萘啶或7-乙酰氨基-2-甲基-1,8-萘啶；
步骤2)中，无需加入任何催化剂；
步骤2)中，升温回流时间为24小时；
步骤2)中，回流温度为150℃。
步骤3)中，得到的沉淀经过滤、用冰甲醇或冰乙醇洗涤、干燥得到亚甲基桥连1,8-萘啶铜(Ⅰ)配合物。
本发明所述亚甲基桥连1,8-萘啶铜(Ⅰ)配合物的应用，将所述亚甲基桥连1,8-萘啶铜(Ⅰ)配合物用作芳基卤化物与咪唑类化合物C―N偶联反应的催化剂。
本发明所述亚甲基桥连1,8-萘啶铜(Ⅰ)配合物用作芳基卤化物与咪唑类化合物C―N偶联反应的催化剂的方法是：将1.0mmol得芳基卤化物、1.0mmol的咪唑、2.0mmol的氢氧化钠、3mL的二甲基亚砜和0.01mmol的亚甲基桥连1,8-萘啶铜(Ⅰ)配合物于100℃下反应。
本领域技术人员可知，通过观察不同条件下对比的实验结果来判断催化效果及催化性能。
本发明的有益效果如下：
1、本发明提供了一种无催化剂条件下通过SP3C―H键活化反应制备亚甲基桥连1,8-萘啶配体的方法，是目前为止发现的第一个实现无催化剂SP3C―H键活化构建C―C键的方法。
2、本发明的无催化剂SP3C―H键活化方法可以简化原料、缩短反应流程，能够实现常规方法难以制备的目标产物，是最经济、最简洁、最高效的途径，符合现代绿色合成化学的发展趋势。
3、本发明提供了一种新型的亚甲基桥连1,8-萘啶铜(Ⅰ)配合物，是目前为止发现的第一个可催化芳基卤化物与咪唑类化合物C―N偶联反应的萘啶铜(Ⅰ)配合物。
4、本发明的配合物可催化芳基卤化物与咪唑类化合物C―N偶联反应，使其应用在有生理活性的天然产物、医药、生物化学、含氮杂环碳烯化学、有机电致发光、太阳能电池光电转化材料等的合成成为可能。
附图说明
图1为配体1在氘代三氯甲烷中的1H-NMR；
图2为配体2在氘代三氯甲烷中的1H-NMR；
图3为亚甲基桥连1,8-萘啶配体及铜(Ⅰ)配合物的合成路线；
图4为亚甲基桥连1,8-萘啶铜(Ⅰ)配合物的晶体结构；
表1为咪唑和溴苯催化N―芳基化反应条件筛选结果；
表2为不同的芳基卤化物和咪唑N―芳基化配合物催化结果。
具体实施方式
为了更清楚地说明本发明，下面结合优选实施例对本发明做进一步的说明。本领域技术人员应当理解，下面所具体描述的内容是说明性的而非限制性的，不应以此限制本发明的保护范围。
实施例
一、亚甲基桥连1,8-萘啶配体及铜(Ⅰ)配合物的合成：
1)合成2-甲基-4-R1-7-乙酰氨基-1,8-萘啶：
在100mL圆底烧瓶中加入7-氨基-2,4-二甲基-1,8-萘啶或7-氨基-2-甲基-1,8-萘啶(4.0g，23.1mmol)，加入15mL乙酸酐，混合物氮气保护下回流反应2h，反应液冷却析出黄色晶体，抽滤得到7-乙酰氨基-2,4-甲基-1,8-萘啶或7-乙酰氨基-2-甲基-1,8-萘啶产物，直接用于下面的反应；
2)无催化剂SP3C―H活化合成亚甲基桥连1,8-萘啶配体：
将0.35g(2.33mmol)邻醛基苯甲酸溶解在30mL N,N-二甲基甲酰胺中，氮气保护下升温至150℃，再加入0.50g(2.32mmol)7-乙酰氨基-2,4-二甲基-1,8-萘啶并继续回流反应24h，停止反应，冷却至室温，真空旋干得黑色固体；使用柱层析硅胶200-300目分离纯化，淋洗剂V乙酸乙酯：V石油醚＝1:1，得淡黄色粉末固体0.36g，产率44.4％。核磁表征见图1，1HNMR(500MHz,CDCl3)δ(ppm)8.58(s,1H NH),8.54(d,J＝9.1Hz,1H),8.41(d,J＝9.0Hz,1H),7.94(d,J＝7.6Hz,1H),7.67(t,J＝7.5Hz,1H),7.56(t,J＝7.5Hz,1H),7.44(d,J＝7.7Hz,1H),7.26(s,1H),6.25(dd,J＝8.7,4.7Hz,1H CH),3.57(dd,J＝14.5,4.6Hz,1H CH2),3.36(dd,J＝14.5,8.8Hz,1H CH2),2.73(s,3H),2.30(s,3H).ESI-MS calcd for C20H17N3O3[M+H]+347.37,found 348.1。
另一亚甲基桥连1,8-萘啶配体合成方法同上，将0.35g(2.33mmol)邻醛基苯甲酸溶解在30mL N,N-二甲基甲酰胺中，氮气保护下升温至150℃，再加入0.46g(2.32mmol)7-乙酰氨基-2-甲基-1,8-萘啶并继续回流反应24h，停止反应，冷却至室温，真空旋干得黑色固体；使用柱层析硅胶200-300目分离纯化，淋洗剂V乙酸乙酯：V石油醚＝1:1，得淡黄色粉末固体0.34g，产率45％。核磁表征见图2,1H NMR(500MHz,CDCl3)δ8.65(s,1H),8.53(d,J＝8.8Hz,1H),8.21(d,J＝8.9Hz,1H),8.12(d,J＝8.2Hz,1H),7.90(d,J＝7.7Hz,1H),7.64(t,J＝7.5Hz,1H),7.53(t,J＝7.5Hz,1H),7.41(t,J＝7.8Hz,2H),6.23(dd,J＝8.5,4.8Hz,1H),3.61(dd,J＝14.5,4.8Hz,1H),3.43(dd,J＝14.5,8.5Hz,1H),2.29(s,3H).ESI-MS calcdfor C19H15N3O3[M+H]+334.34,found 334.1。
3)合成亚甲基桥连1,8-萘啶铜(Ⅰ)配合物：
将亚甲基桥连1,8-萘啶配体(0.072g,0.2mmol)溶于15mL二氯甲烷中，得到A；
称取(39.5mg,0.2mmol)CuI溶于5mL甲醇中，得到B；
将B逐滴加入到A中，滴加过程中能看到溶液由澄清变为黄绿色浑浊，氮气保护室温搅拌反应24小时，得到的沉淀经过滤、用冰甲醇或冰乙醇洗涤，晾干得到黄绿色固体粉末，即为亚甲基桥连1,8-萘啶铜(Ⅰ)配合物。
由于亚甲基桥连1,8-萘啶铜(Ⅰ)配合物的一价铜很容易被氧化为二价铜，二价铜配合物因为具有顺磁性侧不了1HNMR，所以对得到的亚甲基桥连1,8-萘啶铜(Ⅰ)配合物进行质谱和晶体表征。ESI-MS calcd for C40H34CuIN6O6[M-I]+757.18,found 757.4.晶体结构见图4。部分键长：Cu(1)-N(1),Cu(1)-N(4),Cu(1)-I(1),N(1)-C(1),N(1)-C(5),N(2)-C(8),N(2)-C(5),N(3)-C(10),N(3)-C(8),N(4)-C(21),N(4)-C(25),N(5)-C(28),N(5)-C(25),N(6)-C(30),N(6)-C(28)；部分键角：N(1)-Cu(1)-N(4),113.22°；N(1)-Cu(1)-I(1),120.54°；N(4)-Cu(1)-I(1),126.22°；C(1)-N(1)-C(5),117.1°；C(1)-N(1)-Cu(1),126.0°；C(5)-N(1)-Cu(1),113.6°；C(8)-N(2)-C(5),117.7°；C(10)-N(3)-C(8),128.9°；C(21)-N(4)-C(25),117.2°；C(21)-N(4)-Cu(1),123.2°；C(25)-N(4)-Cu(1),115.5°；C(28)-N(5)-C(25),117.1°；C(30)-N(6)-C(28),128.7°；N(1)-C(1)-C(2),122.9°；N(1)-C(1)-C(12),116.7°。
整个反应过程如图3所示。
二、亚甲基桥连1,8-萘啶铜(Ⅰ)配合物用作芳基卤化物与咪唑类化合物C―N偶联反应的催化剂的方法如下：
将1.0mmol得芳基卤化物、1.0mmol的咪唑、2.0mmol的氢氧化钠、3mL的二甲基亚砜和0.01mmol的亚甲基桥连1,8-萘啶铜(Ⅰ)配合物于100℃下反应。
亚甲基桥连1,8-萘啶铜(Ⅰ)配合物催化芳基卤化物与咪唑类化合物C―N偶联反应实验如下：
1、确定本发明的配合物在催化芳基卤化物与咪唑类化合物C―N偶联反应的最佳条件，进行条件筛选。
条件筛选通过配合物催化溴苯与咪唑的C―N偶联反应，通过改变反应条件，包括碱的使用、溶剂使用、反应温度、反应时间、配合物催化剂用量；考察收率，确定最佳催化条件为氢氧化钠作碱(2mmol)、二甲基亚砜作溶剂(3mL)、反应温度为100℃、催化剂即本发明的亚甲基桥连1,8-萘啶铜(Ⅰ)配合物用量0.01mmol，结果见表1。二甲基亚砜作溶剂催化性能较好，收率可达96％，反应时间4h足够，当时间降为2h，收率降至60％；此外，较低温度80℃时，收率仅为82％，催化剂用量为0.5％(摩尔分数)时，反应收率降至70％。
表1咪唑和溴苯催化N―芳基化反应条件筛选结果a
注:a.
反应条件：反应条件:溴苯(1.0mmol)、咪唑(1.0mmol)、碱(2.0mmol)、配合物(0.01mmol)、溶剂(3mL)、空气气氛、b.分离产率；c.使用0.5％(摩尔分数)催化剂。
2、最优反应条件下，取代芳基溴化物和碘化物底物扩展实验：
固定最佳反应条件为：氢氧化钠作碱(2mmol)、二甲基亚砜作溶剂(3mL)、反应温度为100℃、催化剂即亚甲基桥连1,8-萘啶铜(Ⅰ)配合物用量0.01mmol，进行不同取代芳基溴化物和碘化物底物催化扩展实验，结果见表2。该催化体系可容忍各种官能化的芳基卤化物的C―N偶联反应，取代基包括腈基，硝基，乙酰基和醚基等，其中碘化物的催化收率在91％-99％之间。此外，该催化反应具有高选择性，底物为羟基或氨基取代芳基溴化物时，能避免二芳基醚类化合物及二苯胺类化合物的形成。
表2不同的芳基卤化物和咪唑N―芳基化配合物催化结果a
注:a.
反应条件：反应条件:芳基卤化物(1.0mmol)、咪唑(1.0mmol)、氢氧化钠(2.0mmol)、配合物(0.01mmol)、二甲基亚砜(3mL)、100℃空气氛围、b.分离产率；c.2-溴吡啶芳基卤化物。
Claims (7)
1.亚甲基桥连1,8-萘啶配体，其特征在于，分子式为：
其中：R1为甲基。
2.一种亚甲基桥连1,8-萘啶铜(Ⅰ)配合物，其特征在于，用亚甲基桥连1,8-萘啶配体制备的亚甲基桥连1,8-萘啶铜(Ⅰ)配合物，分子式为：
3.如权利要求2所述的亚甲基桥连1,8-萘啶铜(Ⅰ)配合物的制备方法，其特征在于，包括以下步骤：
1)合成2-甲基-4-甲基-7-乙酰氨基-1,8-萘啶：
在圆底烧瓶中加入7-氨基-2,4-二甲基-1,8-萘啶，加入过量乙酸酐，氮气保护下回流2h，薄层色谱检测反应进程，反应液冷却析出黄色晶体，抽滤得到7-乙酰氨基-2,4-甲基-1,8-萘啶产物，直接用于下面的反应；
2)无催化剂SP3C―H活化合成亚甲基桥连1,8-萘啶配体：
在圆底烧瓶中将7-乙酰氨基-2,4-甲基-1,8-萘啶和邻醛基苯甲酸溶解在N,N-二甲基甲酰胺中，氮气保护下升温回流反应，薄层色谱检测反应进程，反应完成后将产物纯化，得亚甲基桥连1,8-萘啶配体。
3)将亚甲基桥连1,8-萘啶配体溶于二氯甲烷中，得到A；
将CuI溶于甲醇中，得到B；
将B逐滴加入到A中，氮气保护搅拌反应24小时，得到沉淀，为亚甲基桥连1,8-萘啶铜(Ⅰ)配合物；其中配体和CuI的摩尔比为1:1。
4.根据权利要求3所述的亚甲基桥连1,8-萘啶铜(Ⅰ)配合物的制备方法，其特征在于，步骤2)中，先溶解邻醛基苯甲酸，回流后再加入7-乙酰氨基-2,4-甲基-1,8-萘啶；无需加入任何催化剂；升温回流时间为24小时；回流温度为150℃。
5.根据权利要求3所述的亚甲基桥连1,8-萘啶铜(Ⅰ)配合物的制备方法，其特征在于，得到的沉淀经过滤、用冰甲醇或冰乙醇洗涤、干燥得到亚甲基桥连1,8-萘啶铜(Ⅰ)配合物。
6.如权利要求2-5任一项所述亚甲基桥连1,8-萘啶铜(Ⅰ)配合物的应用，其特征在于，所述亚甲基桥连1,8-萘啶铜(Ⅰ)配合物用作芳基卤化物与咪唑类化合物C―N偶联反应的催化剂。
7.根据权利要求6所述的亚甲基桥连1,8-萘啶铜(Ⅰ)配合物的应用，其特征在于，所述亚甲基桥连1,8-萘啶铜(Ⅰ)配合物用作芳基卤化物与咪唑类化合物C―N偶联反应的催化剂的方法是：将1.0mmol得芳基卤化物、1.0mmol的咪唑、2.0mmol的氢氧化钠、3mL的二甲基亚砜和0.01mmol的亚甲基桥连1,8-萘啶铜(Ⅰ)配合物于100℃下反应。
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| CN113215584B (zh) * | 2021-04-27 | 2023-02-03 | 上海新阳半导体材料股份有限公司 | 一种化学机械抛光后清洗液的制备方法 |
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